Zorumski C F, Thio L L, Clark G D, Clifford D B
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.
Neuron. 1990 Jul;5(1):61-6. doi: 10.1016/0896-6273(90)90033-c.
Glutamate neurotoxicity is thought to play a role in the pathogenesis of several neurodegenerative diseases. While prolonged activation of either NMDA or non-NMDA receptors causes neuronal damage, NMDA receptors appear to mediate most of the glutamate toxicity. The reasons why NMDA toxicity predominates are uncertain but may relate to more effective neuroprotective mechanisms acting at non-NMDA receptors. To determine whether desensitization is one such mechanism, we studied the effects of the lectin wheat germ agglutinin (WGA) on quisqualate currents and toxicity in cultured postnatal rat hippocampal neurons. After WGA treatment, quisqualate currents exhibit little desensitization and a 4- to 8-fold increase in steady-state amplitude. WGA also markedly augments the degree of acute, quisqualate-induced neuronal degeneration. These results suggest that non-NMDA desensitization serves a neuroprotective function in hippocampal neurons.
谷氨酸神经毒性被认为在几种神经退行性疾病的发病机制中起作用。虽然NMDA或非NMDA受体的长期激活都会导致神经元损伤，但NMDA受体似乎介导了大部分谷氨酸毒性。NMDA毒性占主导地位的原因尚不确定，但可能与作用于非NMDA受体的更有效的神经保护机制有关。为了确定脱敏是否是这样一种机制，我们研究了凝集素麦胚凝集素（WGA）对培养的新生大鼠海马神经元中quisqualate电流和毒性的影响。WGA处理后，quisqualate电流几乎不脱敏，稳态幅度增加4至8倍。WGA还显著增强了急性quisqualate诱导的神经元变性程度。这些结果表明，非NMDA脱敏在海马神经元中发挥神经保护作用。
